Pleural Biphasic Mesothelioma, Pleural Epithelioid Mesothelioma, Stage I Pleural Malignant Mesothelioma AJCC v8, Stage IA Pleural Malignant Mesothelioma AJCC v8, Stage IB Pleural Malignant Mesothelioma AJCC v8, Stage II Pleural Malignant Mesothelioma AJCC v8, Stage IIIA Pleural Malignant Mesothelioma AJCC v8
Conditions
Keywords
Mesothelioma, IMPRINT
Brief summary
This trial studies how well the addition of targeted radiation therapy to surgery and the usual chemotherapy treatment works for the treatment of stage I-IIIA malignant pleural mesothelioma. Targeted radiation therapy such as intensity-modulated radiation therapy or pencil beam scanning uses high energy rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as pemetrexed, cisplatin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving targeted radiation therapy in addition to surgery and chemotherapy may work better than surgery and chemotherapy alone for the treatment of malignant pleural mesothelioma.
Detailed description
PRIMARY OBJECTIVE: I. To detect an improvement in overall survival with the addition of adjuvant hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) to surgery and chemotherapy compared to surgery and chemotherapy alone. SECONDARY OBJECTIVES: I. To determine local failure-free survival, distant-metastases-free survival, and progression-free survival with the addition of adjuvant hemithoracic IMPRINT to surgery and chemotherapy compared to surgery and chemotherapy alone. II. To evaluate the treatment-related toxicities in both arms per Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. III. To detect a clinically meaningful 10-point change in global health status mean scores at 9 months after randomization with the addition of adjuvant IMPRINT as compared to surgery and chemotherapy alone. EXPLORATORY OBJECTIVES: I. To evaluate the degree of under-staging, concordant and upstaging between centrally reviewed clinical staging (based on positron emission tomography (PET), computed tomography (CT) and/or magnetic resonance imaging (MRI)) and pathologic staging. II. To identify immunologic and pathologic biomarkers as predictors of response and potential targets for future combination trials. III. To determine the magnitude of radiation dose escalation to gross residual disease based on combined modality imaging and associated local control rates with dose-painting intensity-modulated radiation therapy (IMRT). IV. To determine the rate of R0/R1 and R2 resections, and type of procedures (extended pleurectomy/decortication \[P/D\], P/D and partial pleurectomy). V. To evaluate the trajectory of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-Q30) and lung cancer specific module (LC13) symptoms in patients treated with IMPRINT by comparing the proportion of patients who respond with quite a bit or very much LC13 symptoms at 9-12 months post-randomization compared to at 3 months post-randomization. VI. To evaluate changes in health-related quality of life, functional domains, and symptoms over time with the addition of adjuvant IMPRINT as compared to surgery and chemotherapy alone. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months for 3 years.
Interventions
DRUGCarboplatin
Intravenously
DRUGCisplatin
Intravenously
PROCEDUREDecortication
Undergo decortication
RADIATIONIntensity-Modulated Radiation Therapy
Daily fractions
DRUGPemetrexed
Intravenously
DRUGPemetrexed Disodium
Intravenously
RADIATIONPencil beam scanning proton therapy
Daily fractions
PROCEDUREPleurectomy
Undergo pleurectomy
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
PRIOR TO STEP 1 REGISTRATION - ALL PATIENTS * Pathologically (histologically or cytologically) confirmed diagnosis of epithelioid or biphasic malignant pleural mesothelioma (MPM) * Imaging proof of clinical stage (American Joint Committee on Cancer \[AJCC\] 8th edition) I-IIIA MPM by PET/CT; * Diagnostic volumetric CT scan of the chest is preferred; however, the CT portion of the PET/CT may be used if CT imaging is of diagnostic quality * MPM is amenable to resection by P/D as determined by a thoracic surgeon * History/physical examination within 42 days prior to Step 1 Registration * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 within 42 days prior to Step 1 Registration * Required Initial Laboratory Values prior to study entry (must be at least 14 days after last infusion of pre-study entry neoadjuvant therapy, if given): * Absolute neutrophil count ≥1500 cells/mm3; * Platelets ≥100,000 cells/mm3; * Hemoglobin ≥ 8.0 g/dL; * Serum total bilirubin ≤ 1.5 X ULN (upper limit of normal); * Aspartate transferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT)) and alanine transaminase (ALT) (serum glutamic-oxaloacetic transaminase (SGPT)) ≤ 3.0 X ULN; * Creatinine clearance ≥45 mL/min by the Cockcroft-Gault (C-G) equation * Negative serum pregnancy test within 14 days of Step 1 Registration for women of childbearing potential * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Note: HIV testing is not required for eligibility for this protocol. * The patient or a legally authorized representative must provide study-specific informed consent prior to study entry PRIOR TO STEP 1 REGISRATION - PATIENTS WHO RECEIVED SYSTEMIC THERAPY BEFORE STUDY ENTRY * The following systemic therapy and immunotherapy combinations are permissible: 1) cisplatin/carboplatin + pemetrexed; 2) cisplatin/carboplatin + pemetrexed + anti-PD-1/L1 agents; and 3) ipilimumab/nivolumab. * Patients must have received at least 2 cycles of neoadjuvant systemic therapy PRIOR TO STEP 2 RANDOMIZATION - ALL PATIENTS * No evidence of progression as defined by PET/CT within 30 days prior to Step 2 randomization. * Patients must have received at least 2 cycles of systemic therapy and undergone a pleurectomy/decortication with the goal of macroscopic complete resection; * ECOG Performance Status 0-1 within 30 days prior to Step 2 Randomization * History/physical examination within 30 days prior to Step 2 Randomization
Exclusion criteria
PRIOR TO STEP 1 REGISTRATION - ALL PATIENTS * Pregnancy or women who are breastfeeding and unwilling to discontinue. * Participants of childbearing potential (participants who may become pregnant or who may impregnate a partner) unwilling to use highly effective contraceptives during and for six months after end of treatment because the treatment in this study may be significantly teratogenic. * Diagnosis of sarcomatoid mesothelioma * Severe, active co-morbidity defined as follows: * New York Heart Association (NYHA) class III or IV heart failure * Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of \> 10 mg prednisone daily or equivalent at the time of registration. Inhaled corticosteroids are allowed; * Unstable angina requiring hospitalization and/or transmural myocardial infarction within the last 3 months; * Interstitial lung disease; * Hemodialysis or peritoneal dialysis; * Concurrent active malignancy (with the exception of current or prior non-melanomatous skin cancer or low-grade malignancies followed observantly for which treatment has not or does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen) * If evidence of disease \< 3 years, institution must consult with the principal investigator, Andreas Rimner, Doctor of Medicine (MD) * Hepatic impairment defined by ChildPugh class (ChildPugh class B & C); * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 30 days prior to registration, if indicated. Note: HBV viral testing is not required for eligibility for this protocol * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 30 days prior to registration * • Active lung infection requiring IV antibiotics * Patients on immunosuppressive therapy, for example history of organ or bone marrow transplant or other hematologic disorders that are expected to compromise life expectancy or tolerance of treatment; * Prior nephrectomy on the contralateral side of MPM * Ipsilateral thoracic electronic implant, e.g. pacemaker, defibrillator, unless switched to the contralateral side prior to initiation of radiation therapy (RT) * Prior thoracic radiation therapy (patients with prior thoracic RT cannot be planned to 50-60 Gy without exceeding normal tissue constraints) * Use of bevacizumab or other antiangiogenic therapy to treat current mesothelioma (due to potential for increased complications from local therapy). * For patients who received neoadjuvant systemic therapy prior to study entry, surgery planned to occur greater than 8 weeks following neoadjuvant systemic therapy PRIOR TO STEP 2 RANDOMIZATION - ALL PATIENTS * Supplemental oxygen use * Third space fluid that cannot be controlled by drainage or insufficient lung expansion after P/D (this prevents targeting the pleura without exceeding normal tissue constraints) * Prior intrapleural therapy (i.e. intrapleural chemotherapy, photodynamic therapy); pleurodesis is permitted * Bulky residual disease in the major fissure preventing pleural IMRT * Patients who have undergone extrapleural pneumonectomy * Patients with active infection that requires systemic I.V. antibiotics, antiviral, or antifungal treatments
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization to the date of death or last follow-up. Maximum follow-up time from randomization was 25 months. | Overall survival was to be estimated by the Kaplan-Meier method and arms were to be compared using a log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive at time of study termination is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant-metastases-free Survival (DMFS) | From randomization to distant failure, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months. | Distant failure (DF) is defined as the appearance of cancer deposits characteristic of metastatic dissemination from mesothelioma. DMFS was to be estimated by the Kaplan-Meier method and arms were to be compared using a log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without failure at time of study termination is reported, and no statistical testing was done. |
| Progression-free Survival (PFS) | From randomization to first progression, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months. | Progression is defined as LE, LF, MF, DF, or death. PFS was to be estimated by the Kaplan-Meier method and arms compared by log-rank test. Analysis was to occur when ≥ 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without progression at study termination is reported, and no statistical testing was done. LE: ≥ 20% increase in the largest diameter (LD) of target lesion from the smallest LD recorded since the treatment start; based on CT scan. LF: Progression of pleural tumor thickness or appearance of a site of pleural thickness \> 5 mm in the site of treated tumor. MF: The appearance of a new measurable site of pleural tumor \> 5mm within the treated site or enlarging tumor dimensions corresponding to a 20% increase in LD compared to initial appearance on imaging evaluation. DF: The appearance of cancer deposits characteristic of metastatic dissemination |
| Number of Patients With Grade 3 or Higher Treatment-related Adverse Event After Randomization | From randomization to death or last follow-up. Maximum follow-up time was 25 months. | Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Adverse events reported as possibly, probably, or definitely related to treatment are considered to be treatment-related adverse events. |
| Change From Randomization to 9 Months in Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) | Randomization and 9 months | Global Health Status is calculated from two questions on the EORTC QLQ-C30. The question responses range from 1 very poor to 7 excellent such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best). |
| Local-failure-free Survival (LFFS) | From randomization to local failure, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months. | Local failure is defined as local enlargement (LE) or local failure (LF) tumor response, marginal failure (MF), or death. LFFS was to be estimated by the Kaplan-Meier method and arms compared by log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without failure at time of study termination is reported, and no statistical testing was done. LE: ≥ 20% increase in the largest diameter (LD) of target lesion from the smallest LD recorded since the treatment start; based on computed tomography (CT) scan. LF: Progression of pleural tumor thickness or appearance of a site of pleural thickness \> 5 mm in the site of treated tumor. MF: The appearance of a new measurable site of pleural tumor \> 5mm within the treated site or enlarging tumor dimensions corresponding to a 20% increase in LD compared to initial appearance on imaging evaluation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Rate of R0/R1 and R2 Resections, by Type of Procedures (Extended Pleurectomy/Decortication (P/D), P/D and Partial Pleurectomy) | Up to 5 years | Proportions of R0/R1 and R2 resections, by type of procedures (extended pleurectomy/decortication (P/D), P/D and partial pleurectomy). |
| Association Between Radiation Dose to Gross Residual Disease and Local Control | Up to 5 years | Gross residual disease and local failure will be analyzed as competing risk data (death without gross residual disease or death without local failure as the respective competing event). Association between radiation dose to gross residual disease and local failure will be evaluated similarly in multivariable analyses using Fine-Gray regression model. |
| Proportion of Patients With Under-staging, Concordant and Upstaging Between Centrally-reviewed Clinical Staging and Pathologic Staging | Up to 5 years | For each subject, the centrally-reviewed clinical staging (based on positron emission tomography, computed tomography and/or magnetic resonance imaging) will be compared with pathologic staging to determine whether it is under-staging (clinical staging is more extensive than pathologic staging), concordant (clinical staging is same as pathologic staging), or upstaging (clinical staging is less extensive than pathologic staging). |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Step 1 Only Patients that did not continue to Step 2 (were not randomized). STEP 1: Patients who received allowed neoadjuvant systemic therapy before study entry undergo pleurectomy/decortication (P/D) within 4 to 8 weeks of systemic therapy. Otherwise, patients undergo P/D within 4 weeks of study entry followed within 4 to 8 weeks by four 21-day cycles of pemetrexed and cisplatin or carboplatin on day 1. | 5 |
| Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) STEP 1: Patients who received allowed neoadjuvant systemic therapy before study entry undergo pleurectomy/decortication (P/D) within 4 to 8 weeks of systemic therapy. Otherwise, patients undergo P/D within 4 weeks of study entry followed within 4 to 8 weeks by four 21-day cycles of pemetrexed and cisplatin or carboplatin on day 1.
STEP 2: Patients receive no treatment. | 5 |
| Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) STEP 1: Same as Arm 1.
STEP 2: Within 4-8 weeks from the end of Step 1 treatment, patients undergo 25-28 fractions of intensity modulated radiation therapy (IMRT) or pencil beam scanning (PBS) proton therapy 5 days/week over 6 weeks. | 6 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Step 1: Registration | Adverse Event | 1 | 0 | 0 |
| Step 1: Registration | Does not meet requirements for Step 2 | 1 | 0 | 0 |
| Step 1: Registration | Study terminated immediately after patient enrolled | 2 | 0 | 0 |
| Step 1: Registration | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Step 1 Only | Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) | Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) | Total |
|---|---|---|---|---|
| Age, Customized ≤ 49 years | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Age, Customized 50 - 59 years | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Age, Customized 60 - 69 years | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Age, Customized ≥ 70 years | 4 Participants | 1 Participants | 2 Participants | 7 Participants |
| Cell type Biphasic mesothelioma | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Cell type Epithelioid | 3 Participants | 4 Participants | 5 Participants | 12 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Registration 0 | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status at Registration 1 | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 4 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Macroscopic complete resection in Step 1 R0 (Complete resection) | — | 1 Participants | 3 Participants | 4 Participants |
| Macroscopic complete resection in Step 1 R1 (Macroscopically complete resection) | — | 3 Participants | 3 Participants | 6 Participants |
| Macroscopic complete resection in Step 1 R2 (Resection that leaves gross tumor behind) | — | 1 Participants | 0 Participants | 1 Participants |
| Pathologic AJCC Stage IA (T1N0M0) | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Pathologic AJCC Stage IIA (T2bN0M0) | 2 Participants | 1 Participants | 4 Participants | 7 Participants |
| Pathologic AJCC Stage IIB (T[1-2]N1M0,T3N0M0) | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Pathologic AJCC Stage IIIA (T[1-2]N2M0) (T3N1M0) (T4N[0-1]M0) | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 2 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Yearly procedure volume at the patient's treatment center < 10 pleurectomy/decortations | — | 1 Participants | 2 Participants | 3 Participants |
| Yearly procedure volume at the patient's treatment center ≥ 10 pleurectomy/decortations | — | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 5 | 2 / 6 |
| other Total, other adverse events | 13 / 13 | 3 / 4 | 3 / 6 |
| serious Total, serious adverse events | 0 / 13 | 0 / 4 | 0 / 6 |
Outcome results
Primary
Overall Survival (OS)
Overall survival was to be estimated by the Kaplan-Meier method and arms were to be compared using a log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive at time of study termination is reported.
Time frame: Randomization to the date of death or last follow-up. Maximum follow-up time from randomization was 25 months.
Population: Randomized patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) | Overall Survival (OS) | 5 Participants |
| Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) | Overall Survival (OS) | 4 Participants |
Secondary
Change From Randomization to 9 Months in Global Heath Status (GHS) Score of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
Global Health Status is calculated from two questions on the EORTC QLQ-C30. The question responses range from 1 very poor to 7 excellent such that a higher response indicates better quality of life (QOL). The mean of these responses is linearly transformed to a range of 0 (worst) to 100 (best).
Time frame: Randomization and 9 months
Population: No patients had both baseline and 9-month data, therefore change from baseline could not be calculated for any patient.
Secondary
Distant-metastases-free Survival (DMFS)
Distant failure (DF) is defined as the appearance of cancer deposits characteristic of metastatic dissemination from mesothelioma. DMFS was to be estimated by the Kaplan-Meier method and arms were to be compared using a log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without failure at time of study termination is reported, and no statistical testing was done.
Time frame: From randomization to distant failure, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months.
Population: Randomized patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) | Distant-metastases-free Survival (DMFS) | 5 Participants |
| Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) | Distant-metastases-free Survival (DMFS) | 2 Participants |
Secondary
Local-failure-free Survival (LFFS)
Local failure is defined as local enlargement (LE) or local failure (LF) tumor response, marginal failure (MF), or death. LFFS was to be estimated by the Kaplan-Meier method and arms compared by log-rank test. Analysis was to occur when at least 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without failure at time of study termination is reported, and no statistical testing was done. LE: ≥ 20% increase in the largest diameter (LD) of target lesion from the smallest LD recorded since the treatment start; based on computed tomography (CT) scan. LF: Progression of pleural tumor thickness or appearance of a site of pleural thickness \> 5 mm in the site of treated tumor. MF: The appearance of a new measurable site of pleural tumor \> 5mm within the treated site or enlarging tumor dimensions corresponding to a 20% increase in LD compared to initial appearance on imaging evaluation.
Time frame: From randomization to local failure, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months.
Population: Randomized patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) | Local-failure-free Survival (LFFS) | 3 Participants |
| Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) | Local-failure-free Survival (LFFS) | 3 Participants |
Secondary
Number of Patients With Grade 3 or Higher Treatment-related Adverse Event After Randomization
Common Terminology Criteria for Adverse Events (version 5.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Adverse events reported as possibly, probably, or definitely related to treatment are considered to be treatment-related adverse events.
Time frame: From randomization to death or last follow-up. Maximum follow-up time was 25 months.
Population: Randomized patients who received protocol treatment and were assessed for adverse events. Arms determined by Step 2 treatment received (as-treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) | Number of Patients With Grade 3 or Higher Treatment-related Adverse Event After Randomization | 0 Participants |
| Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) | Number of Patients With Grade 3 or Higher Treatment-related Adverse Event After Randomization | 1 Participants |
Secondary
Progression-free Survival (PFS)
Progression is defined as LE, LF, MF, DF, or death. PFS was to be estimated by the Kaplan-Meier method and arms compared by log-rank test. Analysis was to occur when ≥ 105 deaths had been reported. Given the small number of participants due to early study closure, only the number of patients last reported to be alive without progression at study termination is reported, and no statistical testing was done. LE: ≥ 20% increase in the largest diameter (LD) of target lesion from the smallest LD recorded since the treatment start; based on CT scan. LF: Progression of pleural tumor thickness or appearance of a site of pleural thickness \> 5 mm in the site of treated tumor. MF: The appearance of a new measurable site of pleural tumor \> 5mm within the treated site or enlarging tumor dimensions corresponding to a 20% increase in LD compared to initial appearance on imaging evaluation. DF: The appearance of cancer deposits characteristic of metastatic dissemination
Time frame: From randomization to first progression, death, or last follow-up, whichever occurs first. Maximum follow-up was 25 months.
Population: Randomized patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Step 1: Chemotherapy, P/D: Step 2: no Treatment) | Progression-free Survival (PFS) | 3 Participants |
| Arm II (Step 1: Chemotherapy, P/D, Step 2: IMRT/PBS) | Progression-free Survival (PFS) | 2 Participants |
Other Pre-specified
Association Between Radiation Dose to Gross Residual Disease and Local Control
Gross residual disease and local failure will be analyzed as competing risk data (death without gross residual disease or death without local failure as the respective competing event). Association between radiation dose to gross residual disease and local failure will be evaluated similarly in multivariable analyses using Fine-Gray regression model.
Time frame: Up to 5 years
Other Pre-specified
Proportion of Patients With Under-staging, Concordant and Upstaging Between Centrally-reviewed Clinical Staging and Pathologic Staging
For each subject, the centrally-reviewed clinical staging (based on positron emission tomography, computed tomography and/or magnetic resonance imaging) will be compared with pathologic staging to determine whether it is under-staging (clinical staging is more extensive than pathologic staging), concordant (clinical staging is same as pathologic staging), or upstaging (clinical staging is less extensive than pathologic staging).
Time frame: Up to 5 years
Other Pre-specified
Rate of R0/R1 and R2 Resections, by Type of Procedures (Extended Pleurectomy/Decortication (P/D), P/D and Partial Pleurectomy)
Proportions of R0/R1 and R2 resections, by type of procedures (extended pleurectomy/decortication (P/D), P/D and partial pleurectomy).
Time frame: Up to 5 years